Transcriptomics

Dataset Information

63

Methylation data from presentation and relapsed medulloblastoma tumour samples


ABSTRACT: We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse. We investigated the DNA methylation profiles of 18 diagnostic and 22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray

ORGANISM(S): Homo sapiens  

SUBMITTER: R M Hill   Ed Schwalbe  S C Clifford  E C Schwalbe 

PROVIDER: E-GEOD-62618 | ArrayExpress | 2015-04-23

SECONDARY ACCESSION(S): GSE62618PRJNA266444

REPOSITORIES: GEO, ArrayExpress

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Publications

Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

Hill Rebecca M RM   Kuijper Sanne S   Lindsey Janet C JC   Petrie Kevin K   Schwalbe Ed C EC   Barker Karen K   Boult Jessica K R JK   Williamson Daniel D   Ahmad Zai Z   Hallsworth Albert A   Ryan Sarra L SL   Poon Evon E   Robinson Simon P SP   Ruddle Ruth R   Raynaud Florence I FI   Howell Louise L   Kwok Colin C   Joshi Abhijit A   Nicholson Sarah Leigh SL   Crosier Stephen S   Ellison David W DW   Wharton Stephen B SB   Robson Keith K   Michalski Antony A   Hargrave Darren D   Jacques Thomas S TS   Pizer Barry B   Bailey Simon S   Swartling Fredrik J FJ   Weiss William A WA   Chesler Louis L   Clifford Steven C SC  

Cancer cell 20141218 1


We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this  ...[more]

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